Breast cancer is one of the most common cancers among women and is the second leading cause of cancer death in women. In 2012, approximately 290,000 new cases of breast cancer were predicted to be diagnosed, and approximately 40,000 women were predicted to die from breast cancer. ErbB2, also known as Her2, is overexpressed in >25% of breast cancers. Patients with ErbB2-overexpressing breast tumors show high recurrence, malignant metastasis, and poor prognosis (Berger, et al., Cancer Res, 48:1238-1243, 1988; Nahta, et al., Nature Clinical Practice, 3:269-280, 2006; Revillion, et al., Eur J Cancer, 34:791-808, 1998; Rohan, et al., Journal of the National Cancer Institute, 90:1262-1269, 1998; Ross, et al., Stem cells, 16:413-428, 1998; Slamon, et al, Science, 235:177-182, 1987; Slamon, et al., Science, 244:707-712, 1989; Yu, et al., Oncogene, 19:6115-6121, 2000).
Because of its critical role in breast tumor growth and progression, ErbB2 has been a target of therapeutic intervention for ErbB2-overexpressing mammary tumors (Nahta, et al., Nature clinical practice, 3:269-280, 2006; Ross, et al., Mol Cell Proteomics, 3:379-398, 2004; Yu, et al., Oncogene, 19:6115-6121, 2000). Effective drugs include trastuzumab and pertuzumab, humanized antibodies directed against the extracellular domain of ErbB2 and lapatinib, an inhibitor of EGFR and ErbB2. However, cancer cells often escape from trastuzumab or lapatinib treatment via intrinsic or de novo pathways (Nahta, et al., Nature clinical practice, 3:269-280, 2006). For example, ErbB2-positive breast tumors may become resistant to trastuzumab, or other antibody therapies, by alternative splicing or by proteolytic cleavage that generate p95HER2, a truncated form of ErbB2, or the extracellular ErbB2 is masked by the membrane-associated glycoprotein mucin-4 (MUC4). Thus, finding alternative treatment approaches is necessary.
Therefore, it is an object of the invention to provide methods and compositions for treating ErbB2-dependent breast cancer.
It is an object of the invention to provide methods and compositions for blocking, inhibiting or reducing the interaction of Erbin and ErbB2.